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This is the largest nationally representative study to date of the toll taken by sepsis and pneumonia, two conditions often caused by deadly microbes, including the antibiotic-resistant bacteria MRSA. Such infections can lead to longer hospital stays, serious complications and even death. "In many cases, these conditions could have been avoided with better infection control in hospitals," said Ramanan Laxminarayan, Ph.D., principal investigator for Extending the Cure, a project examining antibiotic resistance based at the Washington, D.C. think-tank Resources for the Future. "Infections that are acquired during the course of a hospital stay cost the United States a staggering amount in terms of lives lost and health care costs," he said. "Hospitals and other health care providers must act now to protect patients from this growing menace." Laxminarayan and his colleagues analyzed 69 million discharge records from hospitals in 40 states and identified two conditions caused by health care-associated infections: sepsis, a potentially lethal systemic response to infection and pneumonia, an infection of the lungs and respiratory tract. The researchers looked at infections that developed after hospitalization. They zeroed in on infections that are often preventable, like a serious bloodstream infection that occurs because of a lapse in sterile technique during surgery, and discovered that the cost of such infections can be quite high: For example, people who developed sepsis after surgery stayed in the hospital 11 days longer and the infections cost an extra $33,000 to treat per person. Even worse, the team found that nearly 20 percent of people who developed sepsis after surgery died as a result of the infection. "That's the tragedy of such cases," said Anup Malani, a study co-author, investigator at Extending the Cure, and professor at the University of Chicago. "In some cases, relatively healthy people check into the hospital for routine surgery. They develop sepsis because of a lapse in infection control—and they can die." The team also looked at pneumonia, an infection that can set in if a disease-causing microbe gets into the lungs—in some cases when a dirty ventilator tube is used. They found that people who developed pneumonia after surgery, which is also thought to be preventable, stayed in the hospital an extra 14 days. Such cases cost an extra $46,000 per person to treat. In 11 percent of the cases, the patient died as a result of the pneumonia infection.

The North American Spine Society and the Society of Interventional Radiology have pointed to flaws in both studies. And earlier studies, published over 15 years, found major benefits to kyphoplasty and a related procedure called vertebroplasty. "We're missing opportunities for patients to receive a safe and effective treatment that can significantly reduce their pain and disability," said Malamis, an interventional radiologist. The procedures are used to treat vertebral compression fractures in patients with osteoporosis and other conditions that result in brittle bones. In a vertebroplasty, an acrylic cement is injected into a fractured vertebra. In a kyphoplasty, a balloon-tipped catheter first is inserted into the fracture. The balloon is inflated to restore the height and shape of the vertebra before the cement is injected. Neva Nelson, 74, of Naperville, Ill., said a kyphoplasty that Malamis performed in October, 2009, has greatly reduced her pain in a vertebra in her lower back that she fractured after falling on ice. Before her kyphoplasty, Nelson had to sit on cushions. Walking, and especially standing, were painful. "I had to do something," she said. "I could not go on like that." Nelson said that since undergoing her kyphoplasty, "I don't have to worry about my back any more." In the controversial studies, patients were randomly assigned to receive a vertebroplasty or a placebo-like "sham" procedure. In the sham procedure, patients received an injection of anesthetic, but no cement. However, patients in severe pain are reluctant to enroll in a trial where there's a 50 percent chance of receiving a sham treatment. In one of the studies, researchers had to screen 1,813 patients to enroll just 131 subjects. In the other study, only 78 of 219 eligible patients were enrolled. This low enrollment rate raises the possibility that the patients who did enroll were not representative. Patients experience the greatest pain during the first three months after a compression fracture. Thereafter, pain gradually subsides. Thus, a vertebroplasty or kyphoplasty provides the greatest benefit when performed within a week or two of the fracture. But the studies enrolled patients up to 12 months after fractures. In addition to reducing pain and disability, a kyphoplasty can reduce the risk of subsequent fractures by improving the angle and height of the spine. The studies evaluated vertebroplasty alone, and did not include the more innovative and very different kyphoplasty procedure. Malamis suggests the medical community wait for the results of additional studies now underway before passing final judgment on vertebroplasty or kyphoplasty. In the mean time, he notes that Medicare still covers the procedures.

Statistical validation of results, as Shaffer described it, simply involves testing the null hypothesis: that the pattern you detect in your data occurs at random. If you can reject the null hypothesis—and science and medicine have settled on rejecting it when there's only a five percent or less chance that it occurred at random—then you accept that your actual finding is significant. The problem now is that we're rapidly expanding our ability to do tests. Various speakers pointed to data sources as diverse as gene expression chips and the Sloan Digital Sky Survey, which provide tens of thousands of individual data points to analyze. At the same time, the growth of computing power has meant that we can ask many questions of these large data sets at once, and each one of these tests increases the prospects than an error will occur in a study; as Shaffer put it, "every decision increases your error prospects." She pointed out that dividing data into subgroups, which can often identify susceptible subpopulations, is also a decision, and increases the chances of a spurious error. Smaller populations are also more prone to random associations. In the end, Young noted, by the time you reach 61 tests, there's a 95 percent chance that you'll get a significant result at random. And, let's face it—researchers want to see a significant result, so there's a strong, unintentional bias towards trying different tests until something pops out. Young went on to describe a study, published in JAMA, that was a multiple testing train wreck: exposures to 275 chemicals were considered, 32 health outcomes were tracked, and 10 demographic variables were used as controls. That was about 8,800 different tests, and as many as 9 million ways of looking at the data once the demographics were considered.

"Exposure to BPA may be harmful during pregnancy; this exposure may permanently affect the fetus," said Hugh S. Taylor, Ph.D., co-author of the study from Yale University School of Medicine in New Haven, Connecticut. "We need to better identify the effects of environmental contaminants on not just crude measures such as birth defects, but also their effect in causing more subtle developmental errors." Taylor and colleagues made this discovery by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses. Results showed that BPA exposure permanently affected the uterus by decreasing regulation of gene expression. These epigenetic changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure. This suggests that early exposure to BPA genetically "programmed" the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers. BPA has been widely used in plastics and other materials. Examples include use in water bottles, baby bottles, epoxy resins used to coat food cans, and dental sealants. "The BPA baby bottle scare may be only the tip of the iceberg." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Remember how diethylstilbestrol (DES) caused birth defects and cancers in young women whose mothers were given such hormones during pregnancy. We'd better watch out for BPA, which seems to carry similar epigenetic risks across the generations. "